The Role of Complement in Transfusion-Related Acute Lung Injury

Abstract

a b s t r a c tTransfusion-related acute lung injury (TRALI) is a life-threatening complication of acute respiratory distress occurring within 6 hours of blood transfusion. TRALI is one of the leading causes of transfusion-related fatalities and specific therapies are unavailable. Neutrophils are recognized as the major pathogenic cells, whereas T regulatory cells and dendritic cells appear to be important for protection against TRALI. The pathogenesis, however, is complex and incompletely understood. It is frequently postulated that the complement system plays an important role in the TRALI pathogenesis. In this article, we assess the evidence regarding the involvement of complement in TRALI from both human and animal studies. We hypothesize about the potential connection between the complement system and neutrophils in TRALI. Additionally, we draw parallels between TRALI and other acute pulmonary disorders of acute lung injury and acute respiratory distress syndrome regarding the involvement of complement. We conclude that, even though a role for complement in the TRALI pathogenesis seems plausible, studies investigating the role of complement in TRALI are remarkably limited in number and also present conflicting findings. Different types of TRALI animal models, diverse experimental conditions, and the composition of the gastrointestinal microbiota may perhaps all be factors which contribute to these discrepancies. More systematic studies are warranted to shed light on the contribution of the complement cascade in TRALI. The underlying clinical condition of the patient, which influences the susceptibility to TRALI, as well as the transfusion factor (antibody-mediated vs non-antibody-mediated), will be important to take into consideration when researching the contribution of complement. This should significantly increase our understanding of the role of complement in TRALI and may potentially result in promising new treatment strategies.

Post-Traumatic Sepsis Is Associated with Increased C5a and Decreased TAFI Levels

“…Although several studies have reported that a PRBC transfusion can negatively affect clinical outcomes [46,47], it still remains unclear if TAFI is an acute phase reactant that links hemostasis and inflammation or whether it plays an active role in the development of post-traumatic sepsis. With regard to the effects of PRBC transfusions on, e.g., the complement, certain clinical syndromes such as transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) that occur within 6 h of blood transfusions indicate an association [48,49]. The major drivers of those complications and their pathogenesis, however, are complex and incompletely understood.…”

Understanding the role of neutrophils in acute respiratory distress syndrome

“…The antibodies from transfused blood components bind to the pulmonary endothelium followed by accumulation and activation of neutrophils. Activated neutrophils undergo respiratory burst and release ROS, release proteolytic enzymes by degranulation, and form NETs, which further contribute to lung inflammation [ 24 ].…”

Neutrophil Adaptations upon Recruitment to the Lung: New Concepts and Implications for Homeostasis and Disease

“…Bioactive lipids, formed during storage, have also been investigated for their ability to promote TRALI, yielding contradicting results [168,171], further suggesting a role for factors related to donor specificity [172][173][174]. The complement system [175], gut microbiota [176], and other soluble factors, such as osteopontin [177], have also been suggested to play a role in neutrophil accumulation and capillary leakage leading to TRALI. Of note, certain clinical subsets of TRALI do not implicate neutrophils as the key pathogenic cell subset as illustrated by the occurrence of TRALI in neutropenic patients [178,179] and in neutrophil-depleted animal models [180].…”